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Open research questions in Cardiac electrophysiology and arrhythmias

114 unresolved questions extracted from the limitations and future-work sections of 329 Cardiac electrophysiology and arrhythmias papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Further studies are needed to verify the findings, - Investigation of the relationship between QTc interval and MACE in a larger population, - Exploration of the potential mechanisms underlying the association between QTc interval and MACE

    Predictive value of pre-procedural QTc interval for in-hospital major adverse cardiovascular events following primary percutaneous coronary intervention in acute myocardial infarction · 2026 · DOI

  • The relationship between pre-procedural QTc interval and in-hospital MACE is not well understood. Prior studies have not fully explored the predictive value of QTc interval for in-hospital MACE.

    Predictive value of pre-procedural QTc interval for in-hospital major adverse cardiovascular events following primary percutaneous coronary intervention in acute myocardial infarction · 2026 · DOI

  • The paper identifies the challenge of risk stratification in Brugada syndrome, particularly in asymptomatic cases. It highlights the need for accurate risk prediction to avoid premature deaths and unnecessary treatments.

    A Vision Transformer Model for the Prediction of Fatal Arrhythmic Events in Patients with Brugada Syndrome · 2025 · DOI

  • Further research is needed to explore the application of Vision Transformers in other medical imaging domains, - The development of more advanced models that can handle larger and more diverse datasets, - Investigation of the use of Vision Transformers in combination with other techniques, such as convolutional neural networks

    A Vision Transformer Model for the Prediction of Fatal Arrhythmic Events in Patients with Brugada Syndrome · 2025 · DOI

  • In cardiac tissue, reentry underlies many life-threatening cardiac arrhythmias, yet the pathway to initiation of reentry remains incompletely understood.

    Reinforcement learning discovers new mechanisms of reentry in excitable media · 2026 · DOI

  • However, YQHX's regulation of MAMs and associated Ca2+ mechanisms in MI remains unclear.

    Cardioprotective effect of Yiqi Huoxue decoction on post-myocardial infarction injury mediated by Ca2+ flux through MAMs · 2025 · DOI

  • Molecular mechanisms underlying arrhythmias pathogenesis and its progression warrant further investigation.

    Genetic predisposition to immune dysregulation and extracellular matrix remodeling in cardiac arrhythmia reveals potential mediation by SPP1+ macrophages · 2025 · DOI

  • Although the arrhythmic substrate has been hypothesised to be amenable to late Na+ block with ranolazine, the specific mechanisms are not fully understood.

    Effects of ranolazine on the arrhythmic substrate in hypertrophic cardiomyopathy · 2024 · DOI

  • Despite this, the impact of excitation–contraction coupling on the intracellular ATP concentration ([ATP] i ) in myocytes is poorly understood.

    Fueling the heartbeat: Dynamic regulation of intracellular ATP during excitation–contraction coupling in ventricular myocytes · 2024 · DOI

  • The reentrant activity that produces the specific form of VT is not well characterized.

    Mechanisms of torsades de pointes: an update · 2024 · DOI

  • However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear.

    Signal-averaged electrocardiography as a noninvasive tool for evaluating the ventricular substrate in patients with nonischemic cardiomyopathy: reassessment of an old tool · 2024 · DOI

  • However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined.

    Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navβ3 · 2024 · DOI

  • Although well characterized molecularly and clinically in adults, no data have been previously reported on the pediatric population.

    A mild phenotype associated with KCNQ1 p.V205M mediated long QT syndrome in First Nations children of Northern British Columbia: effect of additional variants and considerations for management · 2024 · DOI

  • The paper identifies a gap in the treatment of VT storm, particularly in patients with a normal QT interval. It highlights the need for alternative treatment options for medication-refractory VT storm.

    Treatment of Ventricular Tachycardia Storm with Transvenous Overdrive Pacing in a Patient with a Normal QT Interval · 2026 · DOI

  • The case emphasizes the importance of thoughtful consideration of device strategy in refractory VT management, but lacks systematic guidelines for when to employ overdrive pacing versus other therapeutic modalities.

    Treatment of Ventricular Tachycardia Storm with Transvenous Overdrive Pacing in a Patient with a Normal QT Interval · 2026 · DOI

  • The complexity of Ca2+ signaling in the heart makes it difficult to develop accurate models. The limited availability of data on specific locations of individual IP3R2s relative to RyR2s makes it challenging to develop detailed models.

    Modeling the spatiotemporal properties of crosstalk between RyR-mediated and IP3R-mediated local Ca2+ release · 2026 · DOI

  • The model relies on limited data on specific locations of individual IP3R2s relative to RyR2s. The model uses a simplified representation of the IP3R2 gating mechanism.

    Modeling the spatiotemporal properties of crosstalk between RyR-mediated and IP3R-mediated local Ca2+ release · 2026 · DOI

  • The study addresses the gap in understanding how polygenic risk score modulates T-wave geometry in congenital long-QT syndrome type 1. The study investigates the association between PRS and ECG parameters in a genetically homogeneous cohort of patients with congenital long QT syndrome type 1.

    Polygenic risk modulates myocardial repolarization and T-wave geometry in congenital long-QT syndrome type 1: evidence from digital ECG phenotyping · 2026 · DOI

  • The study has a limited sample size. The recordings were acquired from volunteers in a specific age range. The possibility of residual heart rate-related effects cannot be completely excluded.

    Atrial repolarization wave: a new approach using spline-based feature engineering and explainable AI for atrial arrhythmia diagnosis · 2026 · DOI

  • The atrial repolarization wave remains largely unexplored due to its low amplitude and overlap with the QRS complex. There is a need for a new approach to diagnose atrial arrhythmia using spline-based feature engineering and explainable AI.

    Atrial repolarization wave: a new approach using spline-based feature engineering and explainable AI for atrial arrhythmia diagnosis · 2026 · DOI

  • Limited understanding of clinical risk factors for sudden cardiac death. Limited understanding of the effect of family history of sudden death, history of atrial fibrillation, and anterior infarct location on the development of ventricular fibrillation.

    Risk factors associated with ventricular fibrillation during first ST-elevation myocardial infarction: Individual participant data analysis of 3 prospective case-control studies · 2026 · DOI

  • Even though the 3 studies were all designed specifically to study VF during first STEMI, comprised a large population, and comprehensively phenotyped individuals, our findings should be interpreted considering several limitations, some of which have already been mentioned earlier. Observational studies are always at risk of confounding, and even though we adjusted based on a thorough evaluation of causal pathways, we cannot rule out unmeasured confounding. Only patients who arrived at the hospital and received reperfusion therapy were included in the studies. Thus, some selection bias is pre- sent: patients with VF as their first symptom and/or unwit- nessed cardiac lower probability of resuscitation and survival until hospitalization. As a result, the phenotype of VF cases in this study is not necessarily the same as in all victims to SCD caused by CAD, and results cannot necessarily be extrapolated to populations not included in the study population. arrest have a Patients were interviewed after the event, which increases the risk of recall bias. Patients who have had a cardiac arrest may be more prone to recall SD in their family; however, we believe this risk to be small. After a cardiac arrest, patients may experience retrograde amnesia, or if still comatose, the relatives may be unaware of the immediate circumstances or history. This increases the prevalence of missing data not at random of patients in the case group. Patients using antiar- rhythmic drugs were excluded from the study so results cannot be extrapolated to this subgroup. For example, this might have selected patients with less symptomatic AF, and it is difficult to judge whether results would be the same in in- dividuals receiving, for example, class I or III antiarrhythmic drugs. Finally, the results are vulnerable to misclassification of cases. Postresuscitation ECGs and cardiac enzymes can be difficult to interpret, and deciding whether cardiac arrest judgment. is caused by acute MI demands strong clinical Falsely including cases with a different phenotype, for example, primary arrhythmia or chronic ischemia, could alter the results. Thorough evaluation and adjudication of cases have been done to minimize this effect. Finally, the study is epidemiologic in nature, and further studies are needed to assess genetic, electrical, and mechanistic insights into the ar- rhythmogenesis during acute ischemia.

    Risk factors associated with ventricular fibrillation during first ST-elevation myocardial infarction: Individual participant data analysis of 3 prospective case-control studies · 2026 · DOI

  • To investigate the effects of other factors on the sex difference in TdP risk. To develop a more comprehensive model of cardiac electrophysiology that includes multiple ion channels and cellular processes. To use the computational model to investigate the effects of IKr blockade on cardiac electrophysiology in different patient populations.

    Sex-specific amplification of IKr-blocker-induced action potential prolongation by reduced female IKs repolarization reserve: a computational study using the O'Hara-Rudy human ventricular model · 2026 · DOI

  • The quantitative ionic basis of the sex disparity in Torsades de Pointes risk remains incompletely characterized. The effects of IKr blockade on cardiac electrophysiology in male and female models are not well understood.

    Sex-specific amplification of IKr-blocker-induced action potential prolongation by reduced female IKs repolarization reserve: a computational study using the O'Hara-Rudy human ventricular model · 2026 · DOI

  • This study enhances the understanding of genetic contributions to cJET and suggests further investigation of POPDC2 in other forms of supraventricular tachyarrhythmias.

    Exome Sequencing Identifies POPDC2 as a Candidate Gene for Familial Congenital Junctional Ectopic Tachycardia · 2026 · DOI

Most-cited papers in Cardiac electrophysiology and arrhythmias

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114 open questions have been extracted from the limitations and future-work passages of 329 Cardiac electrophysiology and arrhythmias papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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